This research program is oriented toward investigation of the adenylate cyclase and protein kinase enzyme systems of mammalian and avian kidney. The regulation of these plasma membrane enzymes by parathyroid hormone, calcium and vitamin D metabolites will be investigated. Specifically, the role of these regulatory factors in the genesis of the reduced cyclic AMP response of the kidney to parathyroid hormone in animals maintained on vitamin D deficient or calcium deficient diets will be studied. Kidney responsiveness to parathyroid hormone will be assessed in vivo by measurement of urinary cyclic AMP, phosphate and calcium responses to the hormone and in vitro by measurement of the kidney slice cyclic AMP response to parathyroid hormone and also by assay of the parathyroid hormone-dependent adenylate cyclase of isolated membranes. In addition, an experimental animal model for primary hyperparathyroidism will be studied in order to determine whether or not this experimental animal shows desensitization of the kidney parathyroid hormone-dependent adenylate cyclase activity. Primary hyperparathyroidism will be produced experimentally by implantation of osmotic minipumps in rats. These devices provide constant infusion of bovine parathyroid hormone for studies of the chronic effects of elevated parathyroid hormone on the subsequent kidney cyclic AMP response to this peptide hormone.